1. Field of the Invention
The present invention relates to a spinal nucleus implant to replace all or a portion of nucleus pulposus which has been removed form a spinal disc of a living vertebrate, e.g. a human. This spinal nucleus implant is formed of a xerogel which is capable of anisotropic swelling.
2. Information Disclosure Statement
Spinal intervertebral disc is a cartilaginous tissue located between the endplates of adjacent vertebra. The spinal intervertebral disc acts as a flexible joint between the vertebra, allowing bending and twisting of the spine column. Damage to the spinal intervertebral disc can cause spinal dysfunction, crippling pain and short- or long-term disability. Because of the wide occurrence of this problem (5% annual incidence of back pain due to the spinal intervertebral disc is reported), the economic consequences are enormous. Some disc problems require a surgery. Typical current procedure is fusion of the adjacent vertebra using various techniques and devices, such as those described in the U.S. Pat. No., 4,636,217 (Ogilvie, et al.), U.S. Pat. No. 5,489,308 (Kuslich, et al.) and U.S. Pat. No. 5,716,415 (Steffee). All currently available surgical procedures, such as removal of the nucleus or its part (laminectomy), or fusion of adjacent vertebra, compronise spinal function in one way or another.
For this reason, new remedies are being sought, including the development of prosthesis of the disc or its part. This is a difficult undertaking. The spinal column is an extremely intricate body part, and its proper function is dependent on the seamless cooperation of all its components, including the vertebral discs. A vertebral disc has to perform multiple functions. It has to withstand repeated high stresses in very complex modes of deformation including combined bending, torque, shear and compression. In addition, the spinal intervertebral disc acts as an efficient shock absorber and a pump driving a flow of nutrients into and metabolites from the disc. Structurally, the disc is a rather complex composite part involving several types of materials organized in a complex and intricate fashion. Vertebral endplates are covered by a layer of hyaline cartilage composed of a collagen matrix, a glycoprotein component, and water. In addition, about 2-5% of its volume is occupied by living cells producing the components of the cartilage.
The spinal intervertebral disc itself is composed mainly of crystalline collagen fibrils and amorphous hydrophilic proteoglycans. About 3-5% of the volume is occupied by living cells that produce the its constituents. Structurally, the spinal intervertebral disc is composed of a hydrogel-like core called the nucleus pulposus; and an outside ring called the annulus fibrosus. The structure of the spinal intervertebral disc is schematically depicted in FIG. 1 and described below.
The spinal intervertebral disc acts primarily as a weight-bearing and flexible joint. It enables mutual rotation, bending and translation of the adjacent vertebra, while bearing a considerable axial load. In addition, the spinal intervertebral disc attenuates vibrations and mechanical shocks and prevents their propagation through the skeletal system The load bearing capability and flexibility in selected directions is achieved by the combination of the annulus fibrosus and nucleus pulposus. Annulus fibrosus is a layered structure that is rigid in the radial direction but deformable in the axial direction and by torque. The axial load is born by nucleus pulposus that transforms it partly into an axial component that is contained by the annulus fibrosus. The annulus fibrosus is formed mainly by collagen fibrils organized in several layers. Each layer has its collagen fibrils wound at an angle, and subsequent layers have an alternate orientation. The collagen organization closely resembles organization of fiber reinforcement as in composites used for pressure vessels or cords in tires. It guarantees maximum resistance to radial stress (or internal pressure) while allowing a deformation in torque and bending.
The fibril ends are attached to the adjacent vertebra and to the cartilaginous surface of the vertebral endplates. Consequently, the inner space of the annulus fibrosus is virtually sealed. Any liquid penetrating in or out of the core has to pass through the annulus fibrosus tissue or through the vertebral endplates. To achieve sufficient hydraulic permeability, the collagenous structure of the annulus fibrosus is supplemented by proteoglycans embedded between the collagen fibrils. The proteoglycans are hydrated so that the annulus fibrosus forms a sort of a highly organized, anisotropic hydrogel composite. The collagen domains form a microfibrillar mesh. The result of this arrangement is a sufficient deformability in selected directions combined with high mechanical strength, and particularly high tear strength and resistance to fracture propagation that are needed for a load-bearing function.
The nucleus pulposus is connected to the annulus fibrosus, but not to the endplates. It has much a lower concentration of collagen (which concentration increases with age) and a higher concentration of hydrophilic proteoglycans. Consequently, it is a natural composite which is somewhat like a hydrogel and has a very high equilibrium water content (more than 90% by weight in young persons). The water content and volume of nucleus pulposus depends on osmolarity of swelling medium and on the mechanical pressure. The resistance to the decrease of liquid content due to mechanical pressure is called the "swelling pressure". Swelling pressure is the very key to the function of the nucleus pulposus. As the axial load expels the liquid, the swelling pressure increases until it reaches equilibrium with the external load. Accordingly, the nucleus pulposus is capable of counterbalancing and redistributing the axial stress, converting them to radial components that can be confined by the annulus fibrosus. In addition, the dehydration and rehydration of nucleus pulposus under varying load drives the transport of metabolites and nutrients in and out the spinal intervertebral disc. Therefore, the nucleus pulposus acts as an osmotic pump facilitating transport of nutrient and metabolites to and from the spinal disc and surrounding tissues. This transport function is essential because the cartilaginous components (annulus fibrosus, nucleus pulposus and cartilaginous layer of the vertebral endplates) are neither vascularized nor can be supported with nutrition by mere diffusion.
Since the nucleus pulposus is substantially a macroscopically isotropic tissue, it has to be organized on its molecular and supermolecular levels to perform all these functions.
The nucleus pulposus structure is rather ingenious. The nucleus pulposus is constructed from a two-phase composite consisting of crystalline collagen domains forming a scaffold, and amorphous glycoprotein domains forming hydrophilic filler. The crystalline collagen domains are responsible for a relatively high strength even at high hydration. They form a microfibrillar mesh resembling the fibrous reinforcement in high-performance composites. The result of this arrangement is a sufficient deformability combined with sufficient mechanical strength even at full hydration.
The amorphous domains are responsible for water absorption and for the generation of a swelling pressure. They are formed mainly by high-molecular, water-soluble glycoproteoglycans. Glycoproteoglycans are highly hydrophilic and water-soluble polymers. A small portion of glycoaminoglycans is covalently bound to the coilagenous scaffold, turning it hydrophilic and highly wettable with water (this is necessary for the thermodynamic stability of the two-phase composite). A large portion is unattached to the scaffold and is retained by an entrapment within the scaffold due to the large size of glycoproteoglycans molecules.
To help this physical retention, glycoproteoglycans chains associate to form larger units. Glycoproteoglycans chains are equipped with protein terminal sequences adjusted for attachment to hyaluronic acid. The complexes of the hyaluronic acid and GPG are too large to escape from the collagenous scaffold. This is a very different arrangement than in hydrogels where the confinement of hydrophilic moieties is achieved by crossliking. One can surmise that the arrangement in the nucleus pulposus provides a higher osmotic pressure at a given polymer concentration than the network arrangement usual in hydrogels.
The glycoproteoglycans in the amorphous phase bear a dense negative charge. The high negative charge density is important because it generates high values of viral coefficients and, therefore, causes maximum swelling pressure at a high water content. The high charge density is facilitated by the composite structure of the nucleus pulposus. A synthetic crosslinked hydrogel with a similar charge density would be brittle and mechanically very weak.
A high negative charge is also responsible for a high surface hydration that is necessary for a low wet friction. This is important for the low-friction contact between the nucleus pulposus and the cartilaginous surfaces of vertebral end plates. A high friction would probably cause an excessive wear of the cartilage and degenerative changes in vertebra.
This structural complexity of spinal intervertebral disc is the consequence of complex requirements, not a whimsical excess of nature. Therefore, the disc replacement's function, properties and structure has to be a close approximation of the original disc in order to be able to perform all its functions. In other words, a successful disc replacement has to be biomimetic to the maximum degree achievable.
This was not possible for a long time because there were no synthetic materials that could replicate structure, properties and functions of natural tissue. Because of that, most of the prostheses were designed as mechanical joints enabling certain movement of vertebra but not replicating all SID properties. Such prostheses are described, for instance, in the following U.S. patents:
U.S. Pat. No. 3,875,595 (Froning); U.S. Pat. No. 4,349,921 (Kuntz); U.S. Pat. No. 4,309,777 (Patil); U.S. Pat. No. 4,714,469 (Kenna); U.S. Pat. No. 4,904,261 (Dove, et al.); U.S. Pat. No. 4,759,769 (Hedman, et al.); U.S. Pat. No. 4,863,476 (Shepperd); U.S. Pat. No. 5,053,034 (Olerud); U.S. Pat. No. 5,674,296 (Bryan, et al.); U.S. Pat. No. 5,676,701 (Yuan, et aL); U.S. Pat. No. 5,824,094 (Serhan, et al.); U.S. Pat. No. 5,865,846 (Bryan, et al).
The main problem of these devices is limited functionality. Even more importantly, implantation of these devices is a very complex procedure requiring a major spine surgery with many associated risks, long-term recovery and high cost.
There is an ongoing effort to develop better prosthesis of the disc that would more closely replicate its mechanical function. For instance, Lee et aL in the U.S. Pat. No. 4,911,718 "Functional and Biocompatible Intervertebral Spacer" (1990) describe a composite replacement of the disc made from a biocompatible elastomer reinforced with fibers that mimics the mechanical properties of the natural disc. It replicates the disc structure having an elastomeric core with the shape approximating the shape of nucleus pulposus, wrapped around by a fiber-reinforced elastomeric layers replicating structure of annulus fibrosus. The reinforcing fibers have preferred orientation-simulating arrangement of collagen fibers in annulus fibrosus. The faces of the assembly are equipped with tough elastomeric layers simulating the mechanical function of cartilaginous layers of vertebral endplates. This structure reasonably closely replicates the spinal intervertebral disc structure and its mechanical function. However, the implantation of this device is still very complex and costly, requiring a major spine surgery.
In many cases, the pain relief requires that only nucleus pulposus (or even only its part) be removed rather than whole spinal intervertebral disc. In that case, the major part of the axial load is directly applied to annulus fibrosus. Annulus fibrosus is now stressed by the axial rather than radial load for which it is designed. Consequently, annulus fibrosus delaminates, splits, fractures and brakes down gradually. The situation is somewhat akin to driving on a deflated tire. In this situation, it is useful to replace the missing nucleus pulposus (or its part) to reestablish the radial stress on annulus fibrosus (or to "reinflate" the spinal intervertebral disc) that is required for its proper function. The nucleus pulposus replacement can be carried out by an easier, less traumatic and less expensive surgical procedure.
It is important to recognize that a successful replacement of nucleus pulposus has to replicate not only the mechanical function, but also the function of osmotic pump. Without that, the living tissue of vertebral endplate cartilages and annulus fibrosus cannot be maintained in healthy condition. For those reasons, the nucleus pulposus cannot be replaced by a piece of a hydrophobic, non-hydrogel elastomer, such as silicone rubber or polyurethane.
This need to maintain the liquid transport function was first recognized by Bao et al. in the U.S. Pat. No. 5,047,055. Bao describes a hydrogel prosthesis that has, in its fully hydrated state, the shape and size generally conforming to a missing natural nucleus, i.e., to the cavity left after removal of nucleus pulposus tissue. The hydrogel used in the implant has, in its fully hydrated state, water content at least 30% and compressive strength at least 4 MN/m.sup.2 (i.e., 40 kg/cm.sup.2 or 556 psi). This high strength has to be achieved even at full hydration and at a very high water content, such as in the preferred range 70 to 90% of liquid. Conceivably, this very high requirement on mechanical strength is dictated by possible herniation of isotropic material that was implanted into damaged and weakened annulus fibrosus. This rather extreme requirement limits selection of materials useful for this device, Hydrogels are typically weaker than other plastics and rubbers, particularly at high water content. Therefore, selection of high-swelling hydrogels with such a high compressive strength is rather narrow.
The hydrogel prostheses according to Bao is implanted in partly or fully dehydrated shape when it is undersized, i.e. its volume is 10-70% of the volume of fully hydrated hydrogel implant. Consequently, the hydrogel implant can be inserted through a small incision and then grow into its full size by absorbing aqueous body fluids. The hydrogel used for the implant has in its fully hydrated state water content higher than 30%, and preferably between 70 and 90% of liquid. The materials used by Bao are isotropic so that the implant's expansion due to hydration is equal in all directions. The implant can be composed from 2 or more pieces of combined size and shape, if fully hydrated, of the cavity vacated by the nucleus pulposus removal.
There are several shortcomings of this concept. Hydrogel expansion is limited to the size of the cavity vacated by the nucleus pulposus, so that its swelling pressure at the fully hydrated and expanded state will be very low, or even zero. Therefore, the implant will not generate sufficient axial force for the vertebral separation that can be found in the healthy spinal intervertebral disc. This is different from natural nucleus pulposus that is underswelled inside the spinal intervertebral disc and generates positive swelling pressure even at maximum vertebral separation. Bao could not use such an "oversized design" because the spinal nucleus implant is implanted into a damaged annulus fibrosus (either due to surgical incision or due to the original injury) and expansion of the spinal nucleus implant beyond the cavity size would cause its extrusion similar to herniation of natural nucleus pulposus. As Bao notes, bulging of the implant under stress is prevented by resistance of annulus fibrosus to deformation. Because the integrity of annulus fibrosus is compromised, hydrogel used in prosthesis has to be much stronger than natural nucleus pulposus to resist herniation or extrusion (namely, more than 4 MN/sq.m at full hydration).
This limitation is caused by the fact that the swelling of the Bao's the spinal nucleus implant is isotropic, namely, it is the same in radial and axial directions. Consequently, extensive expansion in axial direction would cause comparable expansion in radial direction that would generate pressure against the damaged annulus fibrosus and cause it rupture, bulging or herniation. In addition, the hydrogels of the kind described by Bao are isotropic elastomers, with the same deformability in any direction. In the described design, the axial load will cause radial deformation, that will be the largest in the direction of the least resistance, i.e. in locations where annulus fibrosus has been weakened by the surgery or by previous injury to the disc. This may result in bulging, herniation or extrusion of the implant--problems similar to the disc damage that was the reason for the surgery in the first place.
Some of these shortcomings were addressed in subsequent invention by Bao et al. described in the U.S. Pat. No. 5,192,326. The prosthetic nucleus is formed by a multiplicity of hydrogel beads having water content at least 30%, said beads being surrounded by a flexible semipermeable cover. The porous cover has, if fully extended, the size and shape of the cavity vacated by the nucleus pulposus removal. The size of the beads is at least three times larger than size of the pores in said cover so that the hydrogel is safely confined within the cover. The hydrogel beads can contain as much as 99% of liquid if fully hydrated. The overall volume of the fully hydrated hydrogel beads may be greater that the volume of the cavity vacated by the nucleus pulposus removal, because casing restricts the swelling and prevents the hydrogel expansion beyond the internal volume and dimensions of the cover. The cover can be made of knitted fibers. Preferably, the casing is coated by a highly biocompatible polymer to prevent adverse reactions to the implant. However, even with a coating the microporous casing may induce a foreign body reaction, initiate protein deposition, become loci of bacterial colonization or cause other problems. The use of the cover sacrifices some advantages of hydrogels, such as high biocompatibility and surface lubricity. In addition, the beads have relatively low packing density and relatively large interstitial space fraction.
Ray et al. invented somewhat similar designs to '326. In the U.S. Pat. No. 4,772,287 Ray describes a implant into the nucleus pulposus composed of two flexible cylindrical bladders filled with a liquid, preferably a thixotropic liquid. The bladders are surrounded by strong fibrous casing, preferably combined with a biodegradable polymer that promotes tissue in growth. Optionally, the bladders are equipped by tubing for adding or withdrawing fluid. This device obviously does not replicate the shape and properties of nucleus pulposus, only attempts to simulate some of its functions. The fibrous casing is designed to facilitate integration of the implant into the residual spinal intervertebral disc tissue, causing thus partial fusion of the vertebral joint.
In the U.S. Pat. No. 4,904,260 Ray describes an improvement of his basic design in which the capsule is made of a semipermeable material and filled with an aqueous liquid containing a therapeutic material capable of a slow diffusion from the implant into the tissue.
In the U.S. Pat. No. 5,674,295 Ray describes another improvement of his basic design in which a hydrogel cylindrical body is used instead of the liquid-filled bladder. The strong fibrous casing is designed to allow more swelling in axial direction than in radial direction, allowing thus sufficient axial expansion while protecting annulus fibrosus against excessive pressure from the expanding and/or deformed hydrogel
This design is further modified in the U.S. Pat. No. 5,824,093 (continuation-in-part to the '295) where the hydrogel bodies have oval crossections and the constraining jacket designed to maintain the general shape of the hydrogel under full hydration and load.
In all Ray's designs the device is not mimicking the nucleus pulposus shape, size, properties or full function. The volume of the hydrated hydrogel is substantially smaller that the natural nucleus pulposus volume. The shape of Ray's implant differs substantially from the nucleus pulposus shape and one could anticipate certain problems with position stability of such implants. To improve the stability, porous or fibrous constraining jacket is incorporated into the residual spinal intervertebral disc tissue. However, this causes a partial fusion, and thus a partial immobilization, of the vertebral joint. The Ray's device does not fill the space designed for nucleus pulposus, which may cause a tendency to distort and to extrude the device under some conditions.
As seen from the description, no prior art invention provides a satisfactory solution to the problem of nucleus pulposus replacement, and neither teaches the present invention nor renders the present invention obvious.
Notwithstanding the prior art, the present invention is neither taught nor rendered obvious thereby.